The long range goals of this project is to contribute to our understanding of the causes and control of diabetes mellitus. The immediate goals are to develop and improve the methods for the chemical synthesis of pure glucagon and its analogs and then to design and synthesize peptides that will be effective inhibitors of the hormone. Such inhibitors ar expected to aid in studies on the mechanism of action of glucagon and to provide an agent for the in vivo regulation of glucagon activity and of blood glucose concentration. The syntheses will be based on the solid phase method, and several recently developed improvements will be incorporated into the proposed new syntheses. The design of the analogs will be based on conformation predictions, X-ray data, NMR and circular dichroism data in dilute solution, and correlations of existing membrane binding and adenyl cyclase activation data.